Robert A. Figlin, MD: Nizar, one of the big challenges that we have in the upfront patient is digesting and interpreting the PISCES trial and the COMPARZ trial, which was a head-to-head, noninferiority trial comparing sunitinib to pazopanib. How do you use that information in your own practice to help the practicing oncologists decide whether it’s going to be one drug or the other?

Nizar M. Tannir, MD, FACP: Sure. I think, first, I’d like to just add to what Sandy and Martin had mentioned about how to choose therapy and when to start therapy in a patient. I think the way I look at it is a patient presenting with advanced disease and primary in situ is different than a patient who had nephrectomy with a curative intent a few years ago and now has recurrent disease. So obviously people who present with advanced disease, that’s an aggressive cancer, so they will require therapy.

I’d like to also mention to add to what was already discussed, the role of metastasectomy surgery still plays an important role. So some of these patients who have low-volume disease in one organ can be managed with surgery before we embark on systemic therapies that are obviously costly as well as toxic.

So back to your question about how do we choose between obviously two good drugs – pazopanib and sunitinib? The two trials that tested these two drugs independently, one, the sunitinib was compared to interferon and the pazopanib was compared to placebo in patients who were either treatment naive or previously treated with cytokines. In these two, phase III trials that were conducted separately, the median progression-free survival with pazopanib and sunitinib was very, very similar.

I think it was around 11 months. So I think that obviously, we had the idea is are these two drugs comparable, and how do we choose in terms of toxicity. We realized early on when pazopanib, which came later, had actually fewer adverse events in our experience when we would treat the patients at MD Anderson with pazopanib. So, it was important to see a phase III trial comparing these two agents that are frontrunners, head to head in the same setting in the same trial. And the COMPARZ was the largest phase III trial that recruited 1,110 patients from all the continents. And the primary endpoint for that trial was progression-free survival and they used a noninferiority design. And the data was clear, pazopanib compared to sunitinib was noninferior and progression-free survival was basically almost the same.

Interestingly, secondary endpoints in the trial looked at quality of life and adverse events, what we refer to as, safety. And compared to sunitinib, pazopanib had a different toxicity profile in many spheres. Using the quality-of-life tools, in 11 out of 16 of these quality-of-life domains, pazopanib had a better quality of life than sunitinib. In terms of adverse events, when we looked at fatigue, stomatitis, and hand-foot skin reaction, certainly pazopanib was, in that regard, better than sunitinib.

So the data and the subsequent phase II trial looking at patient preference as the primary endpoint was a novel and innovative design asking the patients which of the two drugs they prefer. This was a double-blind trial in 169 patients with clear-cell RCC, sunitinib or pazopanib in a blinded fashion and asked them, after 24 weeks, or two blocks of treatment, which of these two agents they preferred. By a 70% to 22% margin, patients picked pazopanib, as the preferred agent, mostly due to the perception that it caused less fatigue.

So these two trials in aggregate, I think, certainly have put pazopanib, as, in my opinion, the preferred agent to use and again, with a caveat that sunitinib was used with a four weeks on, two weeks off schedule which is the approved schedule when sunitinib was approved, giving it on a daily basis four weeks on, two weeks off. So I think there are obviously questions about is sunitinib the best, is that schedule of four weeks on, two weeks off the best schedule to use or would one look at ultimate schedule. I’m sure in the course of this discussion we’ll have chance to discuss that.
Transcript Edited for Clarity

Transcript:

Robert A. Figlin, MD: Nizar, one of the big challenges that we have in the upfront patient is digesting and interpreting the PISCES trial and the COMPARZ trial, which was a head-to-head, noninferiority trial comparing sunitinib to pazopanib. How do you use that information in your own practice to help the practicing oncologists decide whether it’s going to be one drug or the other?

Nizar M. Tannir, MD, FACP: Sure. I think, first, I’d like to just add to what Sandy and Martin had mentioned about how to choose therapy and when to start therapy in a patient. I think the way I look at it is a patient presenting with advanced disease and primary in situ is different than a patient who had nephrectomy with a curative intent a few years ago and now has recurrent disease. So obviously people who present with advanced disease, that’s an aggressive cancer, so they will require therapy.

I’d like to also mention to add to what was already discussed, the role of metastasectomy surgery still plays an important role. So some of these patients who have low-volume disease in one organ can be managed with surgery before we embark on systemic therapies that are obviously costly as well as toxic.

So back to your question about how do we choose between obviously two good drugs – pazopanib and sunitinib? The two trials that tested these two drugs independently, one, the sunitinib was compared to interferon and the pazopanib was compared to placebo in patients who were either treatment naive or previously treated with cytokines. In these two, phase III trials that were conducted separately, the median progression-free survival with pazopanib and sunitinib was very, very similar.

I think it was around 11 months. So I think that obviously, we had the idea is are these two drugs comparable, and how do we choose in terms of toxicity. We realized early on when pazopanib, which came later, had actually fewer adverse events in our experience when we would treat the patients at MD Anderson with pazopanib. So, it was important to see a phase III trial comparing these two agents that are frontrunners, head to head in the same setting in the same trial. And the COMPARZ was the largest phase III trial that recruited 1,110 patients from all the continents. And the primary endpoint for that trial was progression-free survival and they used a noninferiority design. And the data was clear, pazopanib compared to sunitinib was noninferior and progression-free survival was basically almost the same.

Interestingly, secondary endpoints in the trial looked at quality of life and adverse events, what we refer to as, safety. And compared to sunitinib, pazopanib had a different toxicity profile in many spheres. Using the quality-of-life tools, in 11 out of 16 of these quality-of-life domains, pazopanib had a better quality of life than sunitinib. In terms of adverse events, when we looked at fatigue, stomatitis, and hand-foot skin reaction, certainly pazopanib was, in that regard, better than sunitinib.

So the data and the subsequent phase II trial looking at patient preference as the primary endpoint was a novel and innovative design asking the patients which of the two drugs they prefer. This was a double-blind trial in 169 patients with clear-cell RCC, sunitinib or pazopanib in a blinded fashion and asked them, after 24 weeks, or two blocks of treatment, which of these two agents they preferred. By a 70% to 22% margin, patients picked pazopanib, as the preferred agent, mostly due to the perception that it caused less fatigue.

So these two trials in aggregate, I think, certainly have put pazopanib, as, in my opinion, the preferred agent to use and again, with a caveat that sunitinib was used with a four weeks on, two weeks off schedule which is the approved schedule when sunitinib was approved, giving it on a daily basis four weeks on, two weeks off. So I think there are obviously questions about is sunitinib the best, is that schedule of four weeks on, two weeks off the best schedule to use or would one look at ultimate schedule. I’m sure in the course of this discussion we’ll have chance to discuss that.
Transcript Edited for Clarity